In the interval between the submission of the renewal application and the present application for the continuation grant, we have continued to investigate the changes occurring in nuclei and chromatin of resting cells stimulated to proliferate. The studies were carried out on WI-38 human diploid fibroblasts stimulated by serum after reaching confluence. Our investigations have demonstrated that the chromatin of cells stimulated to proliferate undergo changes which include: an increase in chromatin template activity, an increase in the ability to bind intercalating dyes and an increase in the ellipticity in circular dichroism spectra. These changes are abolished when the chromatin of stimulated cells is extracted with low concentrations of salt. We have also shown that similar changes in the function and structure of chromatin occur and are detectable in isolated nuclei. It, therefore, seems that the chromatin mirrors the changes that occur in the nuclei of intact cells. Our studies have also shown that the state of quiescence of cells can be varied by increasing the length of time for which the cells are kept quiescent and, finally, we have shown also that during trypsinization and replating cells there were drastic changes in the content of nuclear proteins. BIBLIOGRAPHIC REFERENCES: Nicolini, Claudio, and Baserga, Renato. Circular Dichroism Spectra and Ethidium Bromide Binding of 5-Deoxybromouridine Substituted Chromatin. Biochem. Biophys. Res. Comm. 64:189-195, 1975. Nicolini, Claudio, Ajiro, Kozk, Borun, Thaddeus, and Renato Baserga. Chromatin Changes During the Cell Cycle of HeLa Cells. J. Biol. Chem. 9:3381-3385, 1975.